Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro

Abstract

A proportion of COVID-19 reconvalescent patients develop post-COVID-19 syndrome (PCS) including a subgroup fulfilling diagnostic criteria of Myalgic  encephalomyelitis/Chronic Fatigue Syndrome (PCS/CFS). Recently, endothelial  dysfunction (ED) has been demonstrated in these patients, but the mechanisms  remain elusive. Therefore, we investigated the effects of patients' sera on  endothelia cells (ECs) in vitro. PCS (n = 17), PCS/CFS (n = 13), and healthy  controls (HC, n = 14) were screened for serum anti-endothelial cell  autoantibodies (AECAs) and dysregulated cytokines. Serum-treated ECs were  analysed for the induction of activation markers and the release of small  molecules by flow cytometry. Moreover, the angiogenic potential of sera was  measured in a tube formation assay. While only marginal differences between  patient groups were observed for serum cytokines, AECA binding to ECs was  significantly increased in PCS/CFS patients. Surprisingly, PCS and PCS/CFS sera  reduced surface levels of several EC activation markers. PCS sera enhanced the  release of molecules associated with vascular remodelling and significantly  promoted angiogenesis in vitro compared to the PCS/CFS and HC groups.  Additionally, sera from both patient cohorts induced the release of molecules  involved in inhibition of nitric oxide-mediated endothelial relaxation. Overall,  PCS and PCS/CFS patients' sera differed in their AECA content and their  functional effects on ECs, i.e., secretion profiles and angiogenic potential. We  hypothesise a pro-angiogenic effect of PCS sera as a compensatory mechanism to ED  which is absent in PCS/CFS patients.